B lymphocytes respond to antigen by proliferating and differentiating into antibody-secreting plasmacytes. That response can be enhanced or inhibited by antigen-specific T-helper (TH) or T-suppressor (TS) cells, respectively. The TNP-specific IgA315-secreting MOPC-315 myeloma plasma cells arise by differentiation from malignant small, nonsecretory lymphocytoid stem cells. The proliferation and differentiation of those stem cells can be regulated by distinct subsets of carrier-specific TH and TS cells. We have found that the TH cell responsible for 315 cell secretory differentiation enhancement is not MHC restricted but is VH restricted. In contrast, the growth-enhancing TH cell population requires the presence of H-2-compatible macrophages to effect help but does not require TH cell: MOPC-315 cell histocompatibility. We have found that the secretory differentiation-enhancing TH cell recognizes not only the carrier that induced it but also a lambda(2)315 idiotope located in the third hypervariable region of VL315. We are presently beginning to characterize the MOPC-315 cell population, which is the target of these regulatory T cells, and to examine the metabolic changes induced in the targets by those regulatory cells. (LB)